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Published on: August 11, 2022
Oestrogenic activity of mimosine on MCF-7 breast cancer cell line through the ERα-mediated pathway
Akm Moyeenul Huq1, Lam Kok Wai1, Kamal Rullah1
1Drug and Herbal Research Centre, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia.
Abstract:
Hormone replacement therapy has been a conventional treatment for postmenopausal symptoms in women. However, it has potential risks of breast and endometrial cancers. The aim of this study was to evaluate the oestrogenicity of a plant-based compound, mimosine, in MCF-7 cells by in silico model. Cell viability and proliferation, ERα-SRC1 coactivator activity and expression of specific ERα-dependent marker TFF1 and PGR genes were evaluated. Binding modes of 17β-oestradiol and mimosine at the ERα ligand binding domain were compared using docking and molecular dynamics simulation experiments followed by binding interaction free energy calculation with molecular mechanics/Poisson-Boltzmann surface area. Mimosine showed increased cellular viability (64,450 cells/ml) at 0.1 μM with significant cell proliferation (120.5%) compared to 17β-oestradiol (135.2%). ER antagonist tamoxifen significantly reduced proliferative activity mediated by mimosine (49.9%). Mimosine at 1 μM showed the highest ERα binding activity through increased SRC1 recruitment at 186.9%. It expressed TFF1 (11.1-fold at 0.1 μM) and PGR (13.9-fold at 0.01 μM) genes. ERα-mimosine binding energy was -49.9 kJ/mol, and it interacted with Thr347, Gly521 and His524 of ERα-LBD. The results suggested that mimosine has oestrogenic activity.
Insights
Mimosine, a plant compound, exhibits estrogenic activity by interacting with the estrogen receptor alpha (ERα). This suggests potential as a safer alternative for postmenopausal symptom treatment compared to traditional hormone replacement therapy.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Hormone replacement therapy (HRT) is a common treatment for postmenopausal symptoms.
- HRT carries risks, including increased breast and endometrial cancer.
- Safer alternatives are needed for managing menopausal symptoms.
Purpose of the Study:
- To evaluate the estrogenic potential of mimosine, a plant-derived compound.
- To investigate mimosine's effects on estrogen receptor alpha (ERα) activity in MCF-7 cells using in silico methods.
Main Methods:
- In silico modeling, including docking and molecular dynamics simulations, was used to assess ERα binding.
- Cell viability, proliferation, and ERα-dependent gene expression (TFF1, PGR) were measured.
- Coactivator (SRC1) recruitment and binding energy calculations were performed.
Main Results:
- Mimosine demonstrated significant cellular viability and proliferation, comparable to 17β-estradiol.
- Mimosine increased ERα-SRC1 coactivator activity and induced expression of ERα-dependent genes TFF1 and PGR.
- Molecular modeling showed strong binding affinity of mimosine to the ERα ligand-binding domain.
Conclusions:
- Mimosine exhibits estrogenic activity, interacting with ERα.
- The findings suggest mimosine as a potential candidate for developing novel therapies for postmenopausal symptoms.
- Further research is warranted to explore mimosine's therapeutic applications and safety profile.
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